Numerous compounds representing a physiological activity have chirality, and thus, are optically active, and it is known in the art that in many cases, two optical isomers in an enantiomeric relationship with each other represent different physiological activities from each other in a human body. In the past, these compounds were commercialized as a racemic mixture form, but nowadays, since a more selective activity is required, technique to separate two enantiomers forming a racemic mixture, and to measure an optical purity of an optically active compound is significantly needed.
Such a difference of the physiological activity is shown as a pharmacological effect in chiral medicine, and thus, more important. Therefore, there is needed the development of technique to separate an optically pure optical isomer by an asymmetric synthesis or optical resolution, and to accurately measure an optical purity, in the course of the development of new medicines.
The separation of the optical isomers includes all methods of separating racemates into pure optical isomers (optical resolution), and of classifying two optical isomers (measurement of optical purity).
As the method for measuring the optical purity of the compound having chirality, chromatographic methods such as gas chromatography and high performance liquid chromatography (HPLC) have been developed. Particularly, the Proton nuclear magnetic resonance (1H-NMR) spectroscopy has received recent attention, for the reasons that an NMR instrument is widespread, as well as an analyte may be recovered, and also since an experiment in a solution state is possible with a small amount of a sample, analysis of both solid and liquid samples is possible. In a method of measuring an optical purity using NMR, the optical purity may be determined by converting a chiral analyte to two diastereomeric compounds using a chiral derivatizing agent (CDA), a chiral lanthanide shift reagent (CLSR), a chiral solvating agent (CSA), or the like, and carrying out analysis through NMR.
Among such methods, a chiral derivatizing agent method has disadvantages in that a derivatization process should be carried out once, and a functional group capable of being derivatized should be present, and a chiral lanthanide shift reagent method has a disadvantage in that a line broadening effect in a spectrum occurs. However, a chiral solvating agent has an advantage in that a non-destructive analysis is directly carried out in an NMR tube so that peak separation of a diastereomeric pairs may be seen, thereby conveniently showing an optical activity, and two diastereomers in an 1H NMR spectrum represent different chemical shifts (δ) from each other, and the optical purity of a chiral compound may be determined using the difference between the integrated values thereof.
Until now, though various chiral solvating agents have been developed, most of them may be used in the measurement of the optical purity of only specific chiral analytes, and thus, they are difficult to be applied to the measurement of the optical purity of a wider range of chiral analytes.